Clinical and Economic Burden During Hospitalizations Among Cancer Patients with Febrile Neutropenia: Evidence From U.S. Hospitals, 2007–2010

Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy that often requires hospitalization. Published burden-of-illness estimates for FN-related hospitalizations were either based on clinical practice more than a decade ago (Caggiano et al Cancer 2005, Kuderer et al Cancer 2006) or derived from small samples (Schilling et al Exp Ther Med 2011).

A retrospective cohort study was conducted to provide updated estimates using 2007–2010 hospital discharge data from a database maintained by Premier and containing service records of over 400 geographically diverse hospitals. It is one of the largest hospital databases in the U.S. The study population included adult patients with 1 of 6 tumor types (breast, lung, colorectal, ovarian cancers; non-Hodgkin lymphoma [NHL]; and Hodgkin lymphoma), discharge diagnoses of neutropenia (ICD-9 code 288.0x) with fever or infection, and receipt of intravenous antibiotics. The average hospitalization cost, case fatality rate, and average length of stay (LOS) associated with each patient's first FN-related hospitalization (index hospitalization) were computed with associated 95% confidence intervals (CIs) for all tumor types combined and stratified by tumor type. Detailed costs and resource utilization components within index hospitalizations were also examined and tallied. Tumor-type-specific multivariate linear regressions (for costs and LOS) and logistic regressions (for mortality) were conducted to assess the effect of infection types and comorbidities on study outcomes, adjusting for other patient and hospital characteristics. FN-related 30-day readmission rates after index hospitalizations were also estimated. All cost measures reflected actual direct costs to hospitals and were adjusted to 2010 dollars.

Hospitalization with FN was identified in 16,273 cancer patients. The mean (SD) age was 63 (14) years; 49% were aged ≥65 years; and 60% were female. Hospitalization costs and clinical outcomes of index hospitalizations varied by tumor type and by discharge status (Table). For all tumor types combined, 19% of patients were treated in an intensive care unit (ICU) setting during index hospitalizations, with average LOS of 5.2 days spent in ICU. The estimated models identified certain infection types and comorbidities as potential risk factors for inpatient mortality and predictors of higher economic burden. Of note, breast cancer patients with diagnosed septicemia/bacteremia (N=656) had average costs that were $5,664 (95% CI: $4,233–$7,095) higher than those with other infections (N=2,623), average LOS that was 1.7 days (95% CI: 1.0–2.3) longer, and a higher case fatality rate (risk ratio [as approximated by odds ratio]: 4.12, 95% CI: 2.6–6.5), after adjusting for other observed potential confounders. Higher average costs were also observed in NHL patients with diagnosed renal disease (N=1,263) than in those without renal disease (N=4,174) (adjusted difference: $10,408, 95% CI: $8,391–$12,425). The FN-related 30-day readmission rate after index hospitalization was 5.9% for all tumor types combined. The rate was 9.9% for NHL and 8.6% for Hodgkin lymphoma, higher than that in patients with other tumor types (2.3%–4.1%).

FN-related hospitalizations among cancer patients are expensive, resource-intensive, and associated with considerable mortality risk. Substantial differences in the clinical and economic burden of FN exist depending on tumor types, infection types, and comorbidities.

Dulisse:Premier healthcare alliance: Employment. Li:Amgen Inc.: Employment, Equity Ownership. Gayle:Premier healthcare alliance: Employment. Barron:Amgen Inc.: Employment, Equity Ownership. Ernst:Premier healthcare alliance, which contracted with Amgen to conduct this study.: Employment. Rothman:Dr. Rothman is an employee of RTI Health Solutions, an independent non-profit research organization that does work for government agencies and pharmaceutical companies.: Employment. Legg:Amgen Inc.: Employment, Equity Ownership. Kaye:RTI Health Solutions (a business unit of RTI International): Employment.